The herpesviruses are the largest and most complex of the known oncogenic DNA viruses. Amongst the human herpesviruses, cytomegalovirus, Epstein-Barr virus and Varicella-zoster virus are the most important but least understood and most difficulat to study. Most adults are seropositive for several of these viruses, and usually harbor them as long-term latent infections in certain neurons or lymphocytes. CMV and VZV can occasionally cause serious clinical disease especially as primary infections in the young or when reactivated in immunodeficient patients, while EBV has been associated with infectious mononucleosis, Burkitt's Lymphoma and nasopharyngeal carcinoma. Although they are all classified in the same group as herpes simplex virus, we find no detectable DNA sequence homology amongst the genomes of HSV, CMV or EBV by sensitive blot hybridization tests. Furthermore, the size and structural organization of their DNA molecules differ markedly from one another. However, these genomes are similar to the extent that all contain various combination and arrangements of inverted duplications or tandem repeat sequences. A precise description and comparison of the location, structure and sequence organization of these repeated regions in EBV, VZV and two subgroups of CMV is the subject of this study. In HSV the inverted repeats are known to encode important regulatory functions expressed at the earliest stages of infection. From a detailed comparison of the structural organization of these genomes we hope to gain insights into 1) The significance and function of the various tandem and inverted repetitive DNA sequences encountered both in herpesviruses and in the genomes of eukaryotic cells in general; 2) The evolutionary divergence of the herpesviruses to produce the different tissue trophisms etc. that lead to diverse disease states and 3) The signals and mechanisms used by herpesviruses to alter and regulate gene expression in the infected host cells.